ClinVar Miner

Submissions for variant NM_194248.3(OTOF):c.5667G>A (p.Trp1889Ter)

gnomAD frequency: 0.00002  dbSNP: rs747471303
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226615 SCV003922455 likely pathogenic Nonsyndromic genetic hearing loss 2023-03-15 criteria provided, single submitter clinical testing Variant summary: OTOF c.5667G>A (p.Trp1889X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar and have been reported in association with non-syndromic deafness in HGMD. The variant allele was found at a frequency of 1.2e-05 in 251390 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5667G>A in individuals affected with Nonsyndromic Hearing Loss And Deafness, Type 9 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003730476 SCV004532300 pathogenic not provided 2024-01-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1889*) in the OTOF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOF are known to be pathogenic (PMID: 18381613, 19250381, 22575033). This variant is present in population databases (rs747471303, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with OTOF-related conditions. ClinVar contains an entry for this variant (Variation ID: 2501018). For these reasons, this variant has been classified as Pathogenic.

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